# Efficacy and safety of tyrosine kinase inhibitors in advanced hepatocellular carcinoma patients with Child-Pugh A and B cirrhosis: a meta-analysis

## TL;DR

This study finds that tyrosine kinase inhibitors work similarly in liver cancer patients with different levels of liver damage, but those with more severe damage face higher risks of serious side effects.

## Contribution

The study provides a meta-analysis comparing the efficacy and safety of tyrosine kinase inhibitors in HCC patients with Child-Pugh A and B cirrhosis.

## Key findings

- No significant differences in overall response rate and disease control rate between Child-Pugh A and B patients.
- Child-Pugh B patients had a borderline higher risk of grade ≥3 treatment-related adverse events.
- TKIs appear effective for both groups, but Child-Pugh B patients may need closer monitoring for toxicity.

## Abstract

Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality. Tyrosine kinase inhibitors (TKIs) are widely used in advanced HCC, yet outcomes may differ by hepatic reserve. We compared the efficacy and safety of guideline-recommended TKIs between patients with Child–Pugh A (CP-A) and Child–Pugh B (CP-B) cirrhosis.

We conducted a PRISMA-guided systematic review and meta-analysis (searches through 15 October 2024). Eligible studies evaluated TKI monotherapy and reported outcomes separately for CP-A and CP-B. Primary endpoints were overall response rate (ORR), disease control rate (DCR), and grade ≥3 treatment-related adverse events (trAEs). Pooled risk ratios (RRs) with 95% CIs were estimated using prespecified random-effects models; small-study effects were explored with funnel plots (and Egger’s test when k ≥ 10).

Twenty-four studies met inclusion. Pooled analyses showed no significant differences between CP-B and CP-A for ORR (k ≈ 15; RR 1.02, 95% CI 0.83–1.27; I2 42.8%) and DCR (k ≈ 10; RR 0.87, 95% CI 0.58–1.29; I2 83.1%). For grade ≥3 trAEs (k ≈ 9), CP-A had a lower risk than CP-B (CP-A vs. CP-B RR 0.79, 95% CI 0.63–1.00; I2 61.7%), indicating a borderline increase in severe toxicity among CP-B. Funnel plots showed no clear asymmetry; Egger’s test for ORR was negative (p = 0.94), and tests were not performed for DCR and trAEs due to k < 10.

In advanced HCC treated with TKI monotherapy, radiologic efficacy (ORR, DCR) appears broadly comparable between CP-B and CP-A, whereas CP-B may experience higher rates of grade ≥3 toxicities. TKIs remain a reasonable option for selected CP-B patients, provided dosing is individualized and adverse events are closely monitored. Prospective, stratified studies are needed to refine patient selection and dose management in CP-B.